It has become possible to probe the renin biosynthetic pathway and to elucidate further the role of renin in experimental and clinical hypertension. My laboratory has developed the means to purify renin from human and canine species in quantities sufficient for detailed biochemical analysis and has derived antirenin antibodies of high specific activity. Thus we plan (1) to better define the renin biosynthetic pathway by continuation of pulse/chase labeling studies and by purification and characterization of a recently isolated large form of renin; (2) to determine the subcellular site of prorenin conversion and to study the enzymatic requirements for conversion as a potential regulatory mechanism in renin release; (3) to extend the direct measurement of renin to human plasma in a variety of clinical conditions as a means to characterize further the spectrum of hypertensive disease; (4) to continue studies using anti-renin antibody as a direct blocking agent in experimental models of hypertension in the primate; and (5) to isolate and purify the renin-like substance recently identified in the brain.